{"title":"Limonene and its metabolite perillyl alcohol inhibit Chlamydia trachomatis growth by altering host isoprenoid metabolism","authors":"Pilar Cebollada, Inés Reigada, Maarit Ylätalo, Candela Gerediaga, Víctor López, Leena Hanski","doi":"10.1007/s13659-026-00611-5","DOIUrl":"10.1007/s13659-026-00611-5","url":null,"abstract":"<div><p>The obligate intracellular bacterium <i>Chlamydia trachomatis</i> is the most common bacterial sexually transmitted infection globally, with approximately 131 million new cases each year. It contributes to widespread reproductive health issues, including infertility and chronic pelvic pain. The unique cell morphology and biphasic life cycle pose challenges to their effective eradication. Guided by the identification of essential oils (EOs) capable of suppressing <i>C. trachomatis</i> intracellular growth, this study evaluated the antichlamydial properties of the monoterpene limonene and its metabolites perillyl alcohol and perilic acid. The antichlamydial activity was assessed through qPCR-based quantification of bacterial genome copy numbers and immunofluorescence staining of chlamydial inclusions to monitor bacterial growth and infectious progeny production. Elementary body membrane integrity was assessed with viability PCR. <i>Citrus limon</i> essential oil exhibited dose-dependent inhibition of <i>C. trachomatis</i> growth, decreasing infectious progeny by over 90%. <i>Pinus sylvestris</i> EO displayed consistent but non-dose-dependent effects. Limonene, a major constituent of the EOs, exhibited significant suppression of chlamydial growth and progeny production, particularly for its R-enantiomer. While viability-PCR data indicated that the EOs and limonene affected EB membrane permeability, EB infectivity was not affected by the treatments. Perillyl alcohol suppressed chlamydial growth at a lower concentration (100 µg mL<sup>−1</sup>) than the parent compound limonene. The antichlamydial activity of both limonene and perillyl alcohol was suppressed when infected cultures were supplemented with farnesyl or geranylgeranyl, indicating that the antichlamydial mechanism of the two monoterpenes involves competitive inhibition of protein prenylation. Hence, targeting host protein prenylation may be an effective antichlamydial strategy.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhong, Chuang Xiao, Yaping Liang, Peng Wang, Yun Long, Shuyi Li, Na Song, Wenbin Shang, Weimin Yang, Xuan Zhang
{"title":"Deacetylforskolin ameliorates bleomycin-induced pulmonary fibrosis by suppressing inflammation and TGF-β1-induced epithelial–mesenchymal transition","authors":"Yan Zhong, Chuang Xiao, Yaping Liang, Peng Wang, Yun Long, Shuyi Li, Na Song, Wenbin Shang, Weimin Yang, Xuan Zhang","doi":"10.1007/s13659-026-00593-4","DOIUrl":"10.1007/s13659-026-00593-4","url":null,"abstract":"<div><p>Pulmonary fibrosis (PF) is a chronic, progressive and irreversible inflammatory disease with limited therapeutic methods in clinic. Deacetylforskolin (DFSK), derived from the plant <i>Coleus forskohlii</i>, is a potent adenylyl cyclase activator with potential anti-inflammatory activity. Herein, we attempted to investigate the therapeutic potential and mechanisms of DFSK against PF in bleomycin (BLM)-induced mouse models and TGF-β1-induced A549 cells. Our results showed that DFSK treatment alleviated lung injury and reduced inflammatory cytokines in a mouse model of BLM-induced acute lung inflammation, an early stage of PF. In a BLM-induced PF mouse model, DFSK attenuated pathological lung injury and collagen deposition, decreased pro-inflammatory cytokines (TNF-α, IL-1β) and profibrotic mediators (TGF-β1, CTGF, hydroxyproline). Upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal marker α-SMA were observed following DFSK treatment. Furthermore, DFSK significantly restored the pulmonary function of PF mice with decreased Te, f, Penh and increased RT, TV. Mechanistically, DFSK suppressed the phosphorylation of JNK and p38 MAPK, and inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) in A549 cells. Collectively, our findings demonstrate that DFSK is an effective therapeutic agent against PF by suppressing inflammation and EMT.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vitor de Souza Mazucato, Winner Duque Rodrigues, Ludmilla Tonani, Marcia Regina von Zeska Kress, Paulo Cezar Vieira
{"title":"GNPS2 molecular networking reveals metabolic diversity in fungi isolated from protease-rich fruits","authors":"Vitor de Souza Mazucato, Winner Duque Rodrigues, Ludmilla Tonani, Marcia Regina von Zeska Kress, Paulo Cezar Vieira","doi":"10.1007/s13659-026-00615-1","DOIUrl":"10.1007/s13659-026-00615-1","url":null,"abstract":"<div><p>Fungi are a rich source of chemical diversity for bioprospecting, yet most of their metabolic potential remains unexplored. This study investigated the metabolic profile of phytopathogenic fungi of the genus <i>Fusarium</i>, isolated from fruits with high protease content, such as papaya and pineapple. Comparative metabolomics was used to evaluate how culture substrates and co-cultivation with the endophyte <i>Neofusicoccum ribis</i> modulate secondary metabolite production. Molecular Networking analysis (GNPS2) revealed an impressive diversity of 173 annotated metabolites, including one previously undescribed compound. Metabolite production was highly dependent on the substrate and fungal strain, showing a strong correlation between phylogeny and metabolic profiles. Several extracts displayed significant inhibitory activity against the protease papain, with some co-cultivation combinations further enhancing this effect. These findings highlight how environmental conditions and microbial interactions activate silent biosynthetic pathways, confirming these fungi as promising sources for bioactive molecule discovery.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00615-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of unprecedented prenylated indole piperazines and pyrazines through cryptic biosynthetic gene cluster heterologous expression","authors":"Ziou Zha, Dan He, Jianguo Song, Zhenhua Guan, Jiapei Han, Chang Liu, Xinyu Wang, Yongchun Zhu, Hucheng Zhu, Wencai Ye, Qin Li, Yonghui Zhang, Yuan Zhou","doi":"10.1007/s13659-026-00601-7","DOIUrl":"10.1007/s13659-026-00601-7","url":null,"abstract":"<div><p>Prenylation modifications of natural products typically introduce greater structural complexity and enhance their biological activities. Yet, the modification of piperazine alkaloids by dimethylallyl tryptophan synthases (DMATS) remains unreported. In this study, we identified and activated a silent DMATS-containing piperazine biosynthetic gene cluster (BGC), <i>flz</i>, in <i>Aspergillus flavipes</i> via heterologous expression and in vitro enzymatic assay, leading to the isolation and identification of sixteen metabolites. Among these, twelve are new, including five tryptophan-valine-derived alkaloids (<b>2</b>–<b>6</b>) and seven previously unreported prenylated analogs (<b>8</b>–<b>13</b>, <b>17</b>). Notably, <b>8</b> and <b>9</b> represent novel prenylated piperazines featuring a unique 6-5-5-6 ring system. Most significantly, we uncovered a versatile DMATS, FlzE, capable of catalyzing mono-prenylation on flexible substrates, such as piperazine, pyrazine, and diketopiperazine, at multiple sites in either regular or reverse manners. This study not only expands the chemical space of indole alkaloid derivatives but also provides a versatile and engineerable biocatalyst for the prenylation of both natural and synthetic products.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00601-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isolation, total synthesis, and biological evaluation of dearomatized isoprenylated acylphloroglucinols from Hypericum przewalskii","authors":"Yong Li, Fei-Fei Xiong, Xiao-Yang Sun, Xing-Ren Li, Dao-Feng Chen, Gang Xu, Yin Nian, Li-Dong Shao","doi":"10.1007/s13659-026-00626-y","DOIUrl":"10.1007/s13659-026-00626-y","url":null,"abstract":"<div><p>New dearomatized isoprenylated acylphloroglucinols hyperprzewones A (<b>1</b>) and B (<b>2</b>) were isolated and characterized from the dried aerial parts of <i>Hypericum przewalskii</i>. The structures of these compounds were confirmed by extensive spectroscopic experiments. A facile synthetic route to <b>1</b> and <b>2</b> was developed via Friedel-Crafts acylation, alkylation, dearomatization, and oxidative [4 + 2] cyclization, giving a 17% overall yield. Moreover, the synthetic derivative <b>8</b> exhibited moderate inhibition on T-type calcium channels Ca<sub>v</sub>3.2.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00626-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shasha Li, Ting Yu, Jianju Feng, Yue Shang, Tao Zhang, Shuzhen Chen, Liyan Yu, Maoluo Gan
{"title":"Pyridone alkaloids from an Antarctic endolichenic Tolypocladium sp.","authors":"Shasha Li, Ting Yu, Jianju Feng, Yue Shang, Tao Zhang, Shuzhen Chen, Liyan Yu, Maoluo Gan","doi":"10.1007/s13659-026-00607-1","DOIUrl":"10.1007/s13659-026-00607-1","url":null,"abstract":"<div><p>Three new pyridone alkaloids, tolypyrone A (<b>1</b>), tolypyrosides A (<b>2</b>) and B (<b>3</b>), and a new tetramic acid 2<i>′</i>-epitolypoalbin (<b>4</b>), along with ten known compounds, were obtained from <i>Tolypocladium</i> sp. CPCC 401485 isolated from an unidentified Antarctic lichen specimen. Structural elucidation of new compounds was achieved by analyses of HRESIMS and NMR spectroscopic data combined with X-ray crystallography, advanced Marfey’s method, and ECD calculation. Tolypyrone A (<b>1</b>) was the first 4-pyridone alkaloid with an unusual octahydro-1<i>H</i>-isochromeno[3,4-<i>b</i>]pyridin-4-one triheterocyclic ring system. Compounds <b>1</b>, <b>4</b> and <b>6</b> exhibited antimicrobial activities with the minimum inhibition concentration of 16−64 μg/mL.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00607-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Xia, Qin Lv, Wei Wang, Meng-Fan Xie, Jin-Cai Li, Kun Li, Dashan Li, Wen-Jing Wang, Li-Dong Shao
{"title":"Advances in natural coumaronochromones: a comprehensive review of natural occurrence, bioactivities, and chemical synthesis","authors":"Dan Xia, Qin Lv, Wei Wang, Meng-Fan Xie, Jin-Cai Li, Kun Li, Dashan Li, Wen-Jing Wang, Li-Dong Shao","doi":"10.1007/s13659-026-00627-x","DOIUrl":"10.1007/s13659-026-00627-x","url":null,"abstract":"<div><p>Coumaronochromones, characterized by a distinctive benzofuro[2,3-<i>b</i>]chromenone core, constitute a rare subclass of isoflavonoids. Biosynthetically, they are proposed to originate from carbohydrate metabolism and the phenylpropanoid pathway like other isoflavones. To date, 92 natural coumaronochromones have been isolated and characterized from nearly 28 species across 24 genera within 7 families (including one fungal source). These compounds are predominantly distributed in the Fabaceae family, which accounts for over half (64%) of all known derivatives. Notably, approximately 20% of coumaronochromones are derived from the genus <i>Euchresta</i> (Fabaceae). The unique scaffold of coumaronochromones confers a broad spectrum of notable pharmacological activities, including anti-inflammatory, antibacterial, insecticidal, cytotoxic, and immunomodulatory effects, highlighting their potential as valuable natural leads for pharmaceutical and agrochemical development. This review comprehensively summarizes recent advances in the chemistry and biology of coumaronochromones, providing a detailed account of their natural occurrence, documented biological activities, and chemical syntheses.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00627-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hidayat Ullah, Huanli Cui, Yu Li, Binghuang Ye, Weijie Peng, Yongdui Ruan, Weibo Dai, Chunling Ma, Xianjing Hu
{"title":"Natural triterpenoid Ardisiacrispin B attenuates colitis-associated cancer via JAK2/STAT3 pathway and gut microbiota modulation","authors":"Hidayat Ullah, Huanli Cui, Yu Li, Binghuang Ye, Weijie Peng, Yongdui Ruan, Weibo Dai, Chunling Ma, Xianjing Hu","doi":"10.1007/s13659-026-00602-6","DOIUrl":"10.1007/s13659-026-00602-6","url":null,"abstract":"<div><p>Colitis-associated cancer (CAC) arises from persistent intestinal inflammation, immune dysregulation, and microbiota-driven epithelial injury, representing a major link between inflammatory bowel disease and colorectal malignancy. Despite advances in therapy, colon cancer remains one of the leading causes of cancer-related mortality worldwide, underscoring the urgent need for effective preventive and immunomodulatory interventions. Ardisiacrispin B (AB), a bioactive triterpenoid isolated from the <i>Ardisia</i> genus, has been reported to suppress tumor growth by regulating apoptosis and ferroptosis; however, its role in inflammation-driven colorectal tumorigenesis remains unexplored. In this study, we investigated the protective and antitumor effects of AB in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mouse model, with a focus on inflammatory signaling pathways, epithelial remodeling, and gut microbiota modulation. AB administration markedly alleviated disease severity, as evidenced by a significant reduction in disease activity index, including body weight loss, diarrhea, and rectal bleeding. Histopathological evaluation revealed preserved colonic mucosal architecture, diminished inflammatory cell infiltration, and a pronounced reduction in tumor number and size. AB treatment partially modulated the gut microbiota, with a trend toward enrichment of beneficial taxa and a reduction in inflammation-associated bacterial populations. Concurrently, AB robustly downregulated the colonic expression of pro-inflammatory cytokines and chemokines. AB treatment was associated with increased expression of pro-apoptotic markers, indicative of enhanced apoptotic signaling in colonic epithelial cells, as indicated by increased expression of cleaved PARP, cleaved caspase-3, p53, and BAX, while markedly inhibiting cellular proliferation through suppression of Ki-67. Mechanistically, AB was associated with attenuation of key inflammatory and oncogenic signaling pathways, including IL-6/JAK2/STAT3, LPS/TLR4/MyD88/NF-κB, and MAPK cascades. Collectively, Ardisiacrispin B attenuates colitis-associated cancer by rebalancing gut microbiota, suppressing inflammation, and inducing tumor cell apoptosis through inhibition of key oncogenic signaling pathways.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00602-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A critical review on the roles of natural products in shaping oral microbiota and preventing chronic diseases","authors":"Yogesh Kumar, Baojun Xu","doi":"10.1007/s13659-026-00605-3","DOIUrl":"10.1007/s13659-026-00605-3","url":null,"abstract":"<div><p>The oral microbiome plays a central role in maintaining both oral and systemic health, and disruptions in its balance can contribute to a wide range of diseases. This review brings together current evidence on how natural products modulate oral microbial communities, promote microbial equilibrium, and help prevent conditions such as dental caries, periodontitis, and chronic systemic disorders linked to oral dysbiosis. Recent studies highlight that phytochemicals particularly polyphenols, terpenoids, saponins, and alkaloids exert antimicrobial, anti-inflammatory, and antioxidant effects that influence bacterial adhesion, biofilm development, gene expression, and acid production. These compounds not only inhibit key oral pathogens but also support beneficial species, helping to sustain a stable and resilient microbiome. Evidence was gathered from PubMed, Scopus, ScienceDirect, and Google Scholar using relevant keywords and focusing on literature from 2015 to 2025. Insights into microbial diversity, environmental influences, host genetics, and advanced sequencing tools further strengthen understanding of oral microbial dynamics. While natural products show strong potential, challenges related to safety, bioavailability, regulatory clarity, and clinical translation remain to explore. This review outlines current progress and future directions needed to transform natural compounds into effective, evidence-based strategies for improving oral and systemic health through microbiome modulation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00605-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147337013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phenazinoates A‒E, five pairs of phenazine conjugates from a mangrove soil-derived Streptomyces strain OUCMDZ-4923","authors":"Dongyang Wang, Peipei Liu, Yukang Gao, Linmeng Chen, Liping Wang, Ning Li, Weiming Zhu","doi":"10.1007/s13659-026-00597-0","DOIUrl":"10.1007/s13659-026-00597-0","url":null,"abstract":"<div><p>Phenazinoates A–E (<b>1</b>–<b>5</b>), comprising five pairs of methyl saphenate conjugates with genistein, <i>o</i>-aminophenol, <i>p</i>-acetaminophenol and glycerol, were isolated from the fermentation broth of mangrove soil-derived <i>Streptomyces</i> sp. OUCMDZ-4923. Their structures were determined through comprehensive one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, coupled with high-resolution electrospray ionization mass spectrometry. The absolute configurations of each isomer were established by comparing experimental electronic circular dichroism spectra with calculated counterparts. Based on the biosynthetic pathway analysis, compounds <b>1</b>‒<b>3</b> were semi-synthesized from the reactions of methyl (<i>R</i>)-saphenate with genistein, <i>o</i>-aminophenol, and <i>o</i>-formamidophenol, utilizing microwave-assisted solid acid catalysis. The compounds were resolved as enantiomerically pure forms and subsequently tested for antibacterial efficacy against six pathogenic bacteria. Phenazinoates A (<b>1</b>) and B (<b>2</b>) demonstrated bioactivity against four Gram-positive bacterial strains, with minimum inhibitory concentration values ranging from 0.78 to 3.13 μg/mL.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00597-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147337065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}